The specific conductance of the epithelium of the reabsorptive duct of the human eccrine sweat gland was determined by cable analysis of microperfused segments of the duct taken from normal (N) and cystic fibrosis (CF) subjects. Conditions were designed to compare the total conductance and relative contributions of Cl, Na, and residual ion conductance components in the two populations. The total conductance (Gt) of the N ducts was 125 +/- 14 mS/cm2, which was sixfold higher than the Gt of CF ducts. Removal of Cl from the media decreased Gt of the N ducts to the same value as that of the CF ducts (15 +/- 2 mS/cm2). Addition of amiloride to the Cl-free perfusate resulted in a further decline in Gt of approximately 5 mS/cm2 in both tissues. However, the effect of amiloride on Gt of the N duct was more than an order of magnitude greater in Cl-containing than in Cl-free media, but its effect on Gt of the CF duct (with or without Cl) was the same as on that of the N duct in Cl-free media. We conclude that the Cl impermeability that is characteristic of the CF tissue is due to the almost complete absence of an electrodiffusive shunt for Cl across this epithelium, while the remaining conductance components are probably not altered.